This project investigates the capacity of a new method of magnetic resonance imaging diffusion spectrum imaging or DSI, to map complex white matter architecture and the neural connectivity in the human brain. This capacity may make it possible ultimately to define the wiring diagram of the brain noninvasively. Current methodology based on diffusion tensor magnetic resonance imaging (DTI) makes it possible to obtain maps that show at each location the mean orientation of white matter, and several research groups including our own, have devised methods to apply tracing procedures to these orientation fields to define the large-scale trajectories of neural pathways. This approach, however, suffers a serious and basic limitation, namely, its inability to describe more than a single orientation at each tissue location. Diffusion spectrum imaging methodology we have recently described overcomes this, providing for the first time an ability to resolve entire distributions white matter orientations at each image location. These maps provide direct descriptions of the interpretation and intersection of cerebral white matter tracts. Accordingly, this project will pursue 3 principal aims: i. To optimize diffusion spectrum imaging for in vivo imaging of cerebral white matter: ii. To validate diffusion spectrum imaging of complex white matter architecture ex vivo (by correlation with confocal microscopy) and in vivo (by correlation with axonal degeneration in patients.), and iii. To measure the accuracy of DSI computation of large scale white matter trajectories, by correlation with known neural pathways defined by functional magnetic resonance imaging (fMRI) in the human visual system.